Water → Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid methyl ester

HRID 417110Notes

Reaction equation

HRID 417110 reaction equation
[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C:22]2[C:23]([O:30][CH3:31])=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)[C:8]([OH:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:34]I.O>CN(C)C=O.C(OCC)(=O)C>[CH3:34][O:9][C:8](=[O:10])[CH:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[N:11]1[C:15]2[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=2[N:13]=[C:12]1[C:22]1[C:23]([O:30][CH3:31])=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66619285Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid

Product 1

HCID 66619331Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5.86 g (13.58 mmol) cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid in 60 ml N,N-dimethylformamide was added 652 mg (14.94 mmol) sodium hydride (55% dispersion in mineral oil) and 2.02 g (14.26 mmol) methyl iodide. The reaction mixture was poured on 300 ml water and 300 ml ethyl acetate and the phases were separated. The aqueous layer was extracted a second time with 300 ml ethyl acetate. The combined organic layers were washed twice with 300 ml water and once with 300 ml brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 60:40). Light yellow solid (88%). MS (Turbo Spray) m/z=446.3 [M+H].

Workup

  1. customthe phases were separated
  2. extractionThe aqueous layer was extracted a second time with 300 ml ethyl acetate
  3. washThe combined organic layers were washed twice with 300 ml water and once with 300 ml brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 60:40)

Sources & evidence

ORD record
ord-36cdbc0e8bef426a972bdc782925017a
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

Loading…